Osteoporotic fractures are the result of low density and especially inferior bone quality (microarchitecture) caused by both internal (genes, hormones) and external (life style) influences. Bone mechanosensors are extremely important for the overall integrity of the skeleton, because in response to mechanical load they activate its modeling, resulting in an increase in bone density and strength. The largest physiological loads are caused by muscle contractions. Bone mass in adult men has a closer relationship to muscle mass than is case in women. The sexual differences in the relationship between bone and muscle mass are also apparent in children. Based on the mechanostatic theory, the muscle-bone unit has been defined as a functional system whose components are under the common control of the hormones of the somatotropin-IGF-I axis, sexual steroids, certain adipose tissue hormones and vitamin D. The osteogenic effects of somatotropin-IGF-I system are based on the stimulation of bone formation, as well as increase in muscle mass. Moreover, somatotropin decreases the bone mechanostat threshold and reinforces the effect of physical stress on bone formation. The system, via the muscle-bone unit, plays a significant role in the development of the childhood skeleton as well as in its stability during adulthood. The muscle and bone are also the targets of androgens, which increase bone formation and the growth of muscle mass in men and women, independently of IGF-I. The role of further above-mentioned hormones in regulation of this unified functional complex is also discussed., I. Žofková., and Obsahuje bibliografii a bibliografické odkazy
Raloxifen is a selective estrogen receptor modulator which prevents bone loss in ovariectomized female mice in a fashion similar to estrogens. Since testosterone-deficient male mice also lose bone mass, we were interested in testing the effects of raloxifen on bones in intact and castrated male mice. Bone density was significantly reduced in castrated animals (1.36±0.04 g/ml) as compared to intact animals (1.42±0.03 g/ml) (p<0.01). When castrated mice with extraordinarily low concentrations of testosterone and with reduced weight of seminal vesicles were treated with raloxifen, the changes in bone density and bone minerals resulting from castration (1.36±0.04 g/ml) were entirely prevented (1.40±0.01 g/ml). Cortical bone was lost in orchidectomized mice, and this decrease in cortical thickness of the femur was prevented by raloxifen administration. Raloxifen in a dose used in humans for treatment of osteoporosis decreased the weight of seminal vesicles, an organ which is highly sensitive to the androgenic effect, decreased the concentration of testosterone (12.5±2.8 μmol/l) (p<0.01) but not to the same level as in the case of castrated animals (0.6±0.3 μmol/l), and did not have any effect on bone density or mineral content in intact mice. The results of the present study may thus be interpreted as supporting the hypothesis that raloxifen is an effective agent against the deleterious effects of castration-induced osteopenia in male mice and also support the hypothesis that estrogens may have physiological skeletal effects in male mice., P. D. Broulík, K. Broulíková., and Obsahuje bibliografii a bibliografické odkazy